Detection of chronic lymphocytic leukemia cell surface markers using surface enhanced Raman scattering gold nanoparticles

Selective targeting and detection of a hematologic malignancy, chronic lymphocytic leukemia, using surface enhanced Raman scattering (SERS) gold nanoparticles is reported. The functional nanoparticles were composed of a gold core onto which an optical reporter dye was adsorbed, protected from aggregation by grafted polyethyleneglycol, and targeted to CD19 antigen by antibodies. The signals were detected by dark-field microscopy and Raman spectrometry. The observation that the Raman signals are not disrupted by several traditional pathology stains indicates advantages over fluorescence methods.     

Near-infrared Raman spectroscopy for optical diagnosis of lung cancer

Raman spectroscopy is a vibrational spectroscopic technique that can be used to optically probe the molecular changes associated with diseased tissues. The objective of our study was to explore near-infrared (NIR) Raman spectroscopy for distinguishing tumor from normal bronchial tissue. Bronchial tissue specimens (12 normal, 10 squamous cell carcinoma (SCC) and 6 adenocarcinoma) were obtained from 10 patients with known or suspected malignancies of the lung. A rapid-acquisition dispersive-type NIR Raman spectroscopy system was used for tissue Raman studies at 785 nm excitation. High-quality Raman spectra in the 700-1,800 cm(-1) range from human bronchial tissues in vitro could be obtained within 5 sec. Raman spectra differed significantly between normal and malignant tumor tissue, with tumors showing higher percentage signals for nucleic acid, tryptophan and phenylalanine and lower percentage signals for phospholipids, proline and valine, compared to normal tissue. Raman spectral shape differences between normal and tumor tissue were also observed particularly in the spectral ranges of 1,000-1,100, 1,200-1,400 and 1,500-1,700 cm(-1), which contain signals related to protein and lipid conformations and nucleic acid's CH stretching modes. The ratio of Raman intensities at 1,445 to 1,655 cm(-1) provided good differentiation between normal and malignant bronchial tissue (p < 0.0001). The results of this exploratory study indicate that NIR Raman spectroscopy provides significant potential for the noninvasive diagnosis of lung cancers in vivo based on the optic evaluation of biomolecules.     

拉曼光谱在癌症组织学诊断中的研究进展

癌症是引发人群死亡率较高的原因之一,尽管医疗技术水平不断地提升,但癌症的早期诊断仍为世界性难题。拉曼光谱作为一种非侵入性的检测方式,具有检测速度快、灵敏度高等独特的优势,有望成为临床癌症早期诊断的新模式。本文综述了国内外学者应用拉曼光谱技术研究人体癌变组织的最新进展,其中包括胃癌、口腔鳞状细胞癌、宫颈癌、鼻咽癌、乳腺癌以及结直肠癌。     

Role of ferroptosis in colorectal cancer

Colorectal cancer(CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer dr...     

The use of Raman spectroscopy to identify and grade prostatic adenocarcinoma in vitro

Raman spectroscopy is an optical technique, which provides a measure of the molecular composition of tissue. Raman spectra were recorded in vitro from both benign and malignant prostate biopsies, and used to construct a diagnostic algorithm. The algorithm was able to correctly identify each pathological group studied with an overall accuracy of 89%. The technique shows promise as a method for objectively grading prostate cancer.     

The use of Raman spectroscopy to differentiate between different prostatic adenocarcinoma cell lines

Raman spectroscopy (RS) is an optical technique that provides an objective method of pathological diagnosis based on the molecular composition of tissue. Studies have shown that the technique can accurately identify and grade prostatic adenocarcinoma (CaP) in vitro. This study aimed to determine whether RS was able to differentiate between CaP cell lines of varying degrees of biological aggressiveness. Raman spectra were measured from two well-differentiated, androgen-sensitive cell lines (LNCaP and PCa 2b) and two poorly differentiated, androgen-insensitive cell lines (DU145 and PC 3). Principal component analysis was used to study the molecular differences that exist between cell lines and, in conjunction with linear discriminant analysis, was applied to 200 spectra to construct a diagnostic algorithm capable of differentiating between the different cell lines. The algorithm was able to identify the cell line of each individual cell with an overall sensitivity of 98% and a specificity of 99%. The results further demonstrate the ability of RS to differentiate between CaP samples of varying biological aggressiveness. RS shows promise for application in the diagnosis and grading of CaP in clinical practise as well as providing molecular information on CaP samples in a research setting.     

结直肠癌患者外周血循环肿瘤细胞的检测及临床研究进展

结直肠癌是最常见的恶性肿瘤之一,虽然综合治疗的开展使其疗效有较大改善,但仍有较多患者死于术后的复发和转移。循环肿瘤细胞(circulating tumor cell,CTC)来源于肿瘤组织,与肿瘤转移及预后密切相关。对CTC检测方法及其在结直肠癌中的临床研究进行综述。     

Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapies

Colorectal cancer (CRC) is one of the cancer models and most of the carcinogenic steps are presently well understood. Therefore, successful preventive measures are currently used in medical practice. However, CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nowadays, pathologic stage is a unique and well-recognized prognostic indicator, however, more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment. Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial. Probably the most important clinical implication of tumor angiogenesis is the development of anti-angiogenic therapy. The goal of this review is to critically evaluate the role of angiogenic markers, assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in anti-angiogenic therapies.     

营养及加速康复外科在结直肠癌围手术期中的应用

目的 探讨围手术期营养治疗及加速康复外科技术在结直肠癌围手术期应用中的可行性和优势。方法  回顾性分 析110例cT1~4a N0~2M0结直肠癌患者资料,根据围手术期措施的不同,分为营养及加速康复组（62例）和传统治疗组（48 例）。营养及加速康复组术前进行营养状况筛查及营养治疗,再进行腹腔镜根治手术,术中予麻醉期间保暖,切口镇痛 泵置入,不留置引流管或早期拔除引流管;术后不置或早期拔除胃肠减压管,鼓励早期协助下床活动及流质饮食,并争取 5 天停静脉补液。传统治疗组则给予一般围手术期处理,对比两组围手术期情况。结果  营养及加速康复组优化措施均可以 顺利进行,术后平均排气时间、输液时间及术后住院时间分别为（2.2±0.8）天、（5.8±1.2）天和（7.8±1.5）天,均较传统 治疗组缩短,差异有统计学意义（P＜0.05）。此外,营养及加速康复组的肺部感染和腹腔感染发生率更低（P＜0.05）, 术后5天内的疼痛评分也更低（P＜0.05）。结论  围手术期营养治疗和加速康复外科技术的应用可加速结直肠癌术后康复。     

Role of circulating free DNA in colorectal cancer

The gradual elucidation of the underlying biology of colorectal cancer has provided new insights and therapeutic options for patients with metastatic disease which are selected according to predictive biomarkers. This precision medicine paradigm, however, is incomplete since not all eligible patients respond to these agents and prognostic stratification is largely based on clinicopathologic variants. Importantly, no robust data exist to help properly select patients with localized disease at high risk for recurrence and most likely to benefit from adjuvant chemotherapy. There is a rapidly expanding body of literature regarding the role of the qualitative and quantitative analysis of circulating free DNA in various neoplasms, which consistently outperforms traditional tumor markers both as a predictive and as a prognostic marker. Several lines of evidence suggest that circulating free DNA may exhibit a complementary role to existing modalities for the early diagnosis of colorectal cancer, the selection of patients for adjuvant chemotherapy, for the follow-up of treated patients, for the selection of treatment for advanced disease and the assessment of response and for determining the prognosis of patients. These data, which are reviewed here, illustrate the important role that circulating biomarkers may soon have at the daily clinical practice.     

表皮生长因子增强二甲基肼诱发大白鼠大肠癌的效力

 本文应用动物诱癌试验观察内源性和外源性表皮生长因子（EGF）对二甲基肼（DMH）诱发WISTAR鼠大肠癌效力的影响。将60只大白鼠随机分咸四组：高EGF组、普通组（对照组）、低EGF组、单EGF组、用DMH连续诱癌20周。结果发现高EGF组动物诱癌阳性率、平均负瘤数、肿瘤平均体积均明显高于普通组，更高于低EGF组（P＜0．05），单EGF组无肿瘤产生。提示EGF可增强DMH诱发WISTRR鼠大肠癌的效力，但不能独立致癌，在本实验中EGF有类似促癌剂的作用。     

Role of exosomal long non-coding RNAs in colorectal cancer

Exosomes are a class of small extracellular vesicles, 30-150 nm in diameter, that transfer biological information (e.g., DNA, RNA, and protein) via cell-to-cell communication. Exosomes play critical roles in the occurrence and development of human cancers, including colorectal cancer (CRC). Recent studies have shown that long non-coding RNAs (lncRNAs) can be encapsulated in exosomes, which transfer lncRNAs from secretory cells into recipient cells. This process affects the progression of CRC, since exosomal lncRNAs display special and extensive functions in CRC tumorigenesis, including malignant proliferation, metastasis, chemoresistance, and inflammatory response. Moreover, due to their specificity and sensitivity, exosomal lncRNAs are released into body fluids (e.g., urine, sputum, and plasma), which have the potential to be biomarkers of CRC tumorigenesis within screening efforts and medical and epidemiologic research. In this review, we aim to clarify the function and mechanism of exosomal lncRNAs in CRC tumorigenesis and provide a strategy for early diagnosis and medical treatment of this malignancy.     

Role of miR-100 in the radioresistance of colorectal cancer cells

The prognosis of radioresistant colorectal cancer (CRC) is generally poor. Abnormal expression of microRNAs (miRNAs) is involved in the radiosensitivity of various tumor cells as these RNAs regulate biological signaling pathways. However, radioresistance-associated miRNAs in CRC have not yet been identified. In this study, we filtered out HCT116 and CCL-244 from seven CRC cell lines that showed the highest difference in radiosensitivity in a clonogenic assay. MiRNA sequencing identified 33 differentially expressed miRNAs (13 up-regulated and 20 down-regulated) in CCL-244 and 37 in HCT116 (20 up-regulated and 17 down-regulated) cells. MiR-100 was significantly down-regulated in CCL-244 cells after X-ray irradiation but not in HCT116 cells. Quantitative real-time PCR showed that the expression of miR-100 in CRC tissues was significantly lower than that in normal tissues. Thus, miR-100 seems to be involved in the radioresistance of CCL-244 cells. MiR-100 up-regulation sensitized CCL-244 cells to X-ray irradiation, which probably led to apoptosis and DNA double-strand breaks in these. In conclusion, to our knowledge, this is the first study to show that miR-100 may play an important role in regulating the radiosensitivity of CRC, and it may act as a new clinical target for CRC radiotherapy.     

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-microm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis.     

The clinical significance of circulating tumor cells in non-metastatic colorectal cancer - A review

Background

Finding a clinical tool to improve the risk stratification and identifying those colorectal cancer patients with an increased risk of recurrence is of great importance. The presence of circulating tumor cells (CTC) in peripheral blood can be a strong marker of poor prognosis in patients with metastatic disease, but the prognostic role of CTC in non-metastatic colorectal cancer is less clear. The aim of this review is to examine the possible clinical significance of circulating tumor cells in non-metastatic colorectal cancer (TNM-stage I-III) with the primary focus on detection methods and prognosis.

Methods

The PubMed and Cochrane database and reference lists of relevant articles were searched for scientific literature published in English from January 2000 to June 2010. We included studies with non-metastatic colorectal cancer (TNM-stage I-III) and CTC detected pre- and/or post-operatively in peripheral blood.

Results

Nine studies qualified for further analyses. Detection rates of CTC in peripheral blood of patients with non-metastatic colorectal cancer varied from 4% to 57%. Seven studies applied RT-PCR and two studies used immunocytochemical methods. Seven studies found the presence of CTC to be a prognostic marker of poor disease-free survival.

Conclusion

The presence of CTC in peripheral blood is a potential marker of poor disease-free survival in patients with non-metastastic colorectal cancer. The low abundance of CTC in non-metastatic colorectal cancer requires very sensitive and specific detection methods. An international consensus on choice of detection method and markers, is warranted before incorporating CTC into risk stratification in the clinical setting.     

Telomere function in colorectal cancer

Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world. Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process. Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length. It is achieved mainly, by telomerase activation. Thus, the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized. Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours. Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis. Taking into account all the results achieved by different groups, quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.     

Optical detection and grading of lung neoplasia by Raman microspectroscopy

The aim of this study was to investigate whether Raman spectroscopy could be used to identify and potentially grade lung neoplasia in cell samples. Normal human bronchial epithelial cells (HBEpCs) were analyzed by Raman spectroscopy and compared with (i) HBEpCs expressing human papillomavirus (HPV) type 16 E7 or CDK4; (ii) the immortalized bronchial epithelial cell line BEP2D and (iii) its asbestos-transformed derivative AsbTB2A. Overall, Raman spectroscopy, in combination with a linear discriminant analysis algorithm, was able to identify abnormal cells with a sensitivity of 91% and a specificity of 75%. Subdivision of the cell types into 3 groups, representing normal cells (HBEpCs), cells with extended lifespan (HBEpCs expressing HPV 16 E7 or CDK4) and immortalized/transformed cells (BEP2D and AsbTB2A) showed that Raman spectroscopy identifies cells in these categories correctly with sensitivities of 75, 79 and 87%, and specificities of 91, 85 and 96%, respectively. In conclusion, Raman spectroscopy can, with high sensitivity, detect the presence of neoplastic development in lung cells and identify the stage of this development accurately, suggesting that this minimally invasive optical technology has potential for lung cancer diagnosis.